EP0553298B1 - Formulation d'aerosol contenant du beclomethasone 17,21 dipropionate - Google Patents

Formulation d'aerosol contenant du beclomethasone 17,21 dipropionate Download PDF

Info

Publication number
EP0553298B1
EP0553298B1 EP92900942A EP92900942A EP0553298B1 EP 0553298 B1 EP0553298 B1 EP 0553298B1 EP 92900942 A EP92900942 A EP 92900942A EP 92900942 A EP92900942 A EP 92900942A EP 0553298 B1 EP0553298 B1 EP 0553298B1
Authority
EP
European Patent Office
Prior art keywords
weight
dipropionate
beclomethasone
percent
amount
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Revoked
Application number
EP92900942A
Other languages
German (de)
English (en)
Other versions
EP0553298A1 (fr
Inventor
Robert K. Schultz
David W. Schultz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
3M Co
Original Assignee
Minnesota Mining and Manufacturing Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=24400688&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP0553298(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Minnesota Mining and Manufacturing Co filed Critical Minnesota Mining and Manufacturing Co
Publication of EP0553298A1 publication Critical patent/EP0553298A1/fr
Application granted granted Critical
Publication of EP0553298B1 publication Critical patent/EP0553298B1/fr
Anticipated expiration legal-status Critical
Revoked legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A61K9/124—Aerosols; Foams characterised by the propellant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders

Definitions

  • This invention pertains to solution aerosol formulations suitable for use in administering drugs.
  • this invention pertains to formulations comprising beclomethasone 17,21 dipropionate.
  • composition aerosol formulations currently use a mixture of liquid chlorofluorocarbons as the propellant.
  • Fluorotrichloromethane, dichlorodifluoromethane and dichlorotetrafluoroethane are the most commonly used propellants in aerosol formulations for administration by inhalation.
  • Hydrofluorocarbon 134a HFC-134a, 1,1,1,2-tetrafluoroethane
  • hydrofluorocarbon 227 HFC-227, 1,1,1,2,3,3,3-heptafluoropropane
  • Beclomethasone 17,21 dipropionate is commercially available as an aerosol product comprising a suspension of a chlorofluorohydrocarbon solvate of beclomethasone 17,21 dipropionate in chlorofluorohydrocarbon propellants. Preparation of the solvate requires several processing Steps and is required in order to obtain a stable aerosol formulation, i.e., one in which the micronized particles of active ingredient remain in the desired respirable particle size range.
  • a solution formulation of beclomethasone 17,21 dipropionate could simplify formulation manufacture and increase the respirable fraction (i.e., the percentage of active ingredient able to reach the airways of the lung where the pharmaceutical effect is exerted).
  • Ethanol is an example of a cosolvent disclosed in this patent.
  • the above formula representing the propellant component generically embraces HFC-134a.
  • European Patent Publication No. 0372777 discloses a self-propelling aerosol formulation which may be free from CFC's which comprises a medicament, 1,1,1,2-tetrafluoroethane, a surface active agent and at least one compound having a higher polarity than 1,1,1,2-tetrafluoroethane.
  • Examples 10 to 12 disclose solution formulations comprising beclomethasone 17,21 dipropionate (0.005g), surface active agent (0.006g), (sorbitan trioleate, oleic acid and lecithin in Examples 10 to 12 respectively), ethanol (1.350g) and 1,1,1,2-tetrafluoroethane (4.040g).
  • the present invention provides an aerosol formulation comprising a therapeutically effective amount of beclomethasone 17,21 dipropionate, a propellant comprising a hydrofluorocarbon selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane, and a mixture thereof, and ethanol in an amount effective to solubilize the beclomethasone 17,21 dipropionate in the propellant, the formulation being further characterized in that Substantially all of the beclomethasone 17,21 dipropionate is dissolved in the formulation, and that the formulation contains no more than 0.0005% by weight of any surfactant.
  • Certain of the preferred formulations of the invention exhibit very desirable chemical stability and provide respirable fractions significantly greater than commercially available beclomethasone 17,21 dipropionate products. Moreover, the formulations of the invention are convenient to manufacture since no solvate of the active ingredient need be prepared.
  • the pharmaceutical solution aerosol formulations of the invention are suitable for pulmonary, buccal, or nasal administration.
  • the medicament beclomethasone 17,21 dipropionate is generally present in a formulation of the invention in a therapeutically effective amount, i.e., an amount such that one or more metered volumes of the formulation contains an amount of drug effective to exert the intended therapeutic action.
  • a therapeutically effective amount i.e., an amount such that one or more metered volumes of the formulation contains an amount of drug effective to exert the intended therapeutic action.
  • the medicament will constitute about 0.02 to about 0.6 percent by weight, more preferably about 0.05 to about 0.5 percent by weight of the total weight of the formulation.
  • Ethanol is generally present in an amount effective to solubilize the beclomethasone 17,21 dipropionate in the propellant.
  • ethanol constitutes about 1 to about 20 percent by weight of the total weight of the aerosol formulation. More preferably, ethanol constitutes about 2 to about 12 percent by weight and even more preferably about 2 to about 10 percent by weight of the aerosol formulation.
  • ethanol will be present in an amount sufficient to dissolve substantially all of the medicament present in the formulation and to maintain the medicament dissolved over the time period and conditions experienced by commercial aerosol products, but not substantially in excess of said amount.
  • Particularly desirable formulations of the invention while not containing amounts of ethanol substantially in excess of that required (during manufacture of the formulation) to dissolve the amount of active ingredient employed, may be subjected to a temperature of -20°C. without precipitation of the active ingredient.
  • the hydrofluorocarbon propellant can be HFC-134a, HFC-227, or a mixture thereof.
  • the propellant preferably constitutes from about 80 to about 99 percent by weight, preferably from about 88 to about 98 percent by weight, and more preferably about 90 to about 98 percent by weight of the total weight of the aerosol formulation.
  • the hydrofluorocarbon propellant is preferably the only propellant present in the formulations of the invention. However, one or more other propellants (e.g., 1-chloro-1,1-difluoroethane) can also be present.
  • the formulations of the invention are substantially free of any surfactant.
  • substantially free as used in the instant specification and claims is meant that the formulations contain no more than 0.0005 percent by weight of a surfactant based on the total weight of the formulation.
  • Preferred formulations contain no surfactant. Presence of a significant amount of a surfactant is believed to be undesirable in the case of solution formulations of beclomethasone 17,21 dipropionate because surfactants such as oleic acid and lecithin seem to promote chemical degradation of the active ingredient when the latter is dissolved in the mixture of HFC-134a and ethanol.
  • Preferred formulations according to the invention consist essentially of beclomethasone 17,21 dipropionate in an amount of about 0.05 to about 0.35 percent by weight based on the weight of the total formulation, ethanol in an amount of about 2 to about 8 percent by weight based on the total weight of the formulation, and 1,1,1,2-tetrafluoroethane.
  • the solution formulations of the invention can be prepared by dissolving the desired amount of beclomethasone 17,21 dipropionate in the desired amount of anhydrous ethanol accompanied by stirring or sonication.
  • the aerosol vial may then be filled using conventional cold-fill or pressure-fill methods.
  • Formulations containing the following ingredients (TABLE I) in the indicated amounts were prepared with the percentages being expressed in parts by weight based upon the total weight of the particular formulation.
  • the active ingredient employed in preparing the formulations of Examples 2, 3, and 5 - 7 was beclomethasone dipropionate, USP while that employed in preparing the formulations of Examples 1 and 4 was a conventional trichloromonofluoromethane solvate of beclomethasone dipropionate.
  • the formulations of Examples 1, 4, 5 and 6 were prepared by i) dissolving the active ingredient in the ethanol; ii) metering the solution obtained above into an aluminum vial and crimping a continuous valve onto the vial; iii) pressure-filling the vial with 1,1,1,2-tetrafluoroethane; iv) chilling the vial to -60°C.; and v) replacing the continuous valve with a 50 microliter valve which is available under the trade designation "W303-98" from 3M.
  • Examples 2, 3 and 7 were prepared by i) dissolving the active ingredient in the ethanol; ii) metering the solution obtained above into an aluminum vial and crimping a 50 microliter pressure-fill valve which is available under the trade designation SpraymiserTM M3652 from 3M onto the vial; and iii) pressure-filling the vial with 1,1,1,2-tetrafluoroethane.
  • the actuator employed in the case of all the formulations was a solution actuator available under the trade designation "M3756” from 3M.
  • the elastomer employed in the valves in the case of all formulations was that available under the trade designation "DB-218" from American Gasket and Rubber Co. (Chicago, IL.) TABLE I Ingredient Example 1 2 3 4 5 6 7 Beclomethasone 17,21 Dipropionate 0.1% 0.1% 0.25% 0.3% 0.4% 0.44% 0.5% Ethanol (anhydrous) 3% 5% 10% 5% 10% 10% 15% 1,1,1,2-Tetrafluoroethane 96.9% 94.9% 89.75% 94.7% 89.6% 89.56% 84.5%
  • Example 4 The chemical stability of the formulation of Example 4 was determined in respect to recovery of the active ingredient over time when the formulation was stored at 40°C. TABLE II contains the data. TABLE II Storage Time (Weeks) 0 2 4 7 12 % Recovery 101.4, 101.9, 100.8, 99.3, 100.6 98.7 101.6 99.6 95.5 102.6
  • Example 1 did not exhibit precipitation of the active ingredient on freezing to -60°C.
  • the respirable fraction provided by the formulations of Examples 1 - 7 was determined using an Anderson MK II Cascade Impactor with the average respirable fraction obtained from each being in excess of 40%. In the case of the formulations of Examples 1 and 4, the respirable fraction was about 76% and about 70%, respectively.
  • the optimum amount of active ingredient for low and high strength products would be about 0.08 and 0.34 percent by weight, respectively, based on the total weight of the formulations.
  • a mixture containing 1.67 g of beclomethasone 17,21 dipropionate and 160g of cold (-65°C) ethanol was homogenized using a Virtis 45 homogenizer.
  • the resulting suspension was placed in a one gallon stainless steel filling vessel equipped with a stir bar.
  • a 1839 g portion of cold (-65°C) 1,1,1,2-tetrafluoroethane was added to the filling vessel. After about 5 minutes of stirring, a solution was obtained.
  • the resulting formulation contained 0.08 percent by weight of beclomethasone 17,21 dipropionate, 8.0 percent by weight of ethanol and 91.92 percent by weight of 1,1,1,2-tetrafluoroethane.
  • the formulation was cold filled into aerosol vials and then 50 ⁇ L cold fill valves were crimped onto the vials.
  • Example 8 Using the general method of Example 8, a formulation containing 0.34 percent by weight of beclomethasone 17,21 dipropionate, 8.0 percent by weight of ethanol and 91.66 percent by weight of 1,1,1,2-tetrafluoroethane was prepared. The formulation was cold filled as a suspension into aerosol vials which were then equipped with 50 ⁇ L cold fill valves. The formulation changed from a suspension to a solution as the vials warmed to room temperature.
  • a formulation containing 0.3 percent by weight of beclomethasone 17,21 dipropionate, 10 percent by weight of ethanol and 89.7 percent by weight of 1,1,1,2,3,3,3-heptafluoropropane was prepared by i) weighing a 30 mg portion of beclomethasone 17,21 dipropionate into an aerosol vial ii) crimping a continuous valve onto the vial and iii) pressure filling with a solution containing 10 percent ethanol in 1,1,1,2,3,3,3-heptafluoropropane.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Dispersion Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Otolaryngology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Claims (13)

  1. Formulation d'aérosol comprenant une quantité thérapeutiquement efficace de 17,21-dipropionate de beclométhasone, un agent de propulsion comprenant un hydrofluorocarbone choisi dans le groupe comprenant le 1,1,1,2-tétrafluoroéthane, le 1,1,1,2,3,3,3-heptafluoropropane et un mélange de ceux-ci, et de l'éthanol en une quantité efficace pour solubiliser le 17,21-dipropionate de beclométhasone dans l'agent de propulsion, la formulation étant de plus caractérisée en ce que essentiellement la totalité du 17,21-dipropionate de beclométhasone est dissoute dans la formulation et en ce que la formulation ne contient pas plus de 0,0005 % en poids d'agent tensioactif.
  2. Formulation d'aérosol en solution suivant la revendication 1, comprenant entre 0,02 et environ 0,6 % en poids de 17,21-dipropionate de beclométhasone, entre environ 1 et environ 20 % en poids d'éthanol et entre environ 80 et environ 99 % en poids de l'agent de propulsion susdit.
  3. Formulation d'aérosol en solution suivant la revendication 1, dans laquelle le 17,21-dipropionate de beclométhasone est présent en une quantité d'environ 0,05 à environ 0,5 % en poids.
  4. Formulation d'aérosol en solution suivant la revendication 1, dans laquelle l'éthanol est présent en une quantité d'environ 2 à environ 12 % en poids.
  5. Formulation d'aérosol en solution suivant la revendication 1, dans laquelle l'éthanol est présent en une quantité d'environ 2 à 10 % en poids.
  6. Formulation d'aérosol en solution suivant la revendication 1, dans laquelle l'agent de propulsion est présent en une quantité d'environ 88 à environ 98 % en poids.
  7. Formulation d'aérosol en solution suivant la revendication 1, comprenant du 1,1,1,2-tétrafluoroéthane comme essentiellement le seul agent de propulsion.
  8. Formulation d'aérosol en solution suivant la revendication 1, comprenant du 1,1,1,2,3,3,3-heptafluoropropane comme essentiellement le seul agent de propulsion.
  9. Formulation d'aérosol en solution suivant la revendication 1, comprenant du 17,21-dipropionate de beclométhasone en une quantité d'environ 0,05 à environ 0,5 % en poids, de l'éthanol en une quantité d'environ 2 à environ 12 % en poids et l'agent de propulsion en une quantité d'environ 88 à environ 98 % en poids.
  10. Formulation d'aérosol en solution suivant la revendication 1, comprenant du 17,21-dipropionate de beclométhasone en une quantité d'environ 0,05 à environ 0,45 % en poids, de l'éthanol en une quantité d'environ 2 à environ 10 % en poids et l'agent de propulsion en une quantité d'environ 90 à environ 98 % en poids.
  11. Formulation d'aérosol en solution suivant la revendication 1, se composant essentiellement de 17,21-dipropionate de beclométhasone en une quantité d'environ 0,05 à environ 0,35 % en poids, d'éthanol en une quantité d'environ 2 à environ 8 % en poids et de 1,1,1,2-tétrafluoroéthane.
  12. Formulation d'aérosol en solution suivant la revendication 1, dans laquelle la quantité d'éthanol présente n'est pas sensiblement en excès de la quantité requise pour dissoudre essentiellement la totalité du 17,21-dipropionate de beclométhasone mais est suffisante pour permettre à la formulation d'être soumise à une température de -20°C sans une précipitation importante du 17,21-dipropionate de beclométhasone.
  13. Procédé de préparation d'une formulation d'aérosol en solution comprenant l'étape consistant à combiner une quantité thérapeutiquement efficace de 17,21-dipropionate de beclométhasone, d'un agent de propulsion choisi dans le groupe comprenant le 1,1,1,2-tétrafluoroéthane, le 1,1,1,2,3,3,3-heptafluoropropane et un mélange de ceux-ci, et d'une quantité d'éthanol efficace pour solubiliser le 17,21-dipropionate de beclométhasone dans l'agent de propulsion.
EP92900942A 1990-10-18 1991-10-09 Formulation d'aerosol contenant du beclomethasone 17,21 dipropionate Revoked EP0553298B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US59969490A 1990-10-18 1990-10-18
US599694 1990-10-18
PCT/US1991/007574 WO1992006675A1 (fr) 1990-10-18 1991-10-09 Formulation d'aerosol contenant du beclomethasone 17,21 dipropionate

Publications (2)

Publication Number Publication Date
EP0553298A1 EP0553298A1 (fr) 1993-08-04
EP0553298B1 true EP0553298B1 (fr) 1994-11-17

Family

ID=24400688

Family Applications (1)

Application Number Title Priority Date Filing Date
EP92900942A Revoked EP0553298B1 (fr) 1990-10-18 1991-10-09 Formulation d'aerosol contenant du beclomethasone 17,21 dipropionate

Country Status (12)

Country Link
EP (1) EP0553298B1 (fr)
JP (2) JP2769925B2 (fr)
AT (1) ATE114112T1 (fr)
AU (1) AU658854B2 (fr)
BR (1) BR1100339A (fr)
CA (1) CA2094266C (fr)
DE (1) DE69105212T2 (fr)
DK (1) DK0553298T3 (fr)
ES (1) ES2064160T3 (fr)
HK (1) HK130397A (fr)
NZ (1) NZ240237A (fr)
WO (1) WO1992006675A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6433040B1 (en) 1997-09-29 2002-08-13 Inhale Therapeutic Systems, Inc. Stabilized bioactive preparations and methods of use
US6565885B1 (en) 1997-09-29 2003-05-20 Inhale Therapeutic Systems, Inc. Methods of spray drying pharmaceutical compositions
US6638495B2 (en) 1997-09-29 2003-10-28 Nektar Therapeutics Stabilized preparation for use in metered dose inhalers
US7101534B1 (en) 1991-12-18 2006-09-05 3M Innovative Properties Company Suspension aerosol formulations
US7220403B2 (en) 1999-09-11 2007-05-22 Glaxo Group Limited Pharmaceutical formulation of fluticasone propionate
US8371292B2 (en) 2003-09-16 2013-02-12 Nycomed Gmbh Use of ciclesonide for the treatment of respiratory diseases
US8404217B2 (en) 2000-05-10 2013-03-26 Novartis Ag Formulation for pulmonary administration of antifungal agents, and associated methods of manufacture and use
US8435497B2 (en) 2003-06-13 2013-05-07 Takeda Gmbh Formoterol of and ciclesonide combination
US8709484B2 (en) 2000-05-10 2014-04-29 Novartis Ag Phospholipid-based powders for drug delivery
US8715623B2 (en) 2001-12-19 2014-05-06 Novartis Ag Pulmonary delivery of aminoglycoside
US8877162B2 (en) 2000-05-10 2014-11-04 Novartis Ag Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery
US9554993B2 (en) 1997-09-29 2017-01-31 Novartis Ag Pulmonary delivery particles comprising an active agent

Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8828477D0 (en) 1988-12-06 1989-01-05 Riker Laboratories Inc Medical aerosol formulations
DE4123663A1 (de) * 1991-07-17 1993-01-21 Schwabe Willmar Gmbh & Co Aerosol-zubereitung und verwendung eines treibmittels dafuer
US5653962A (en) * 1991-12-12 1997-08-05 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicaments
ES2079210T3 (es) * 1991-12-12 1996-01-01 Glaxo Group Ltd Formulacion farmaceutica de aerosol.
US5674471A (en) * 1991-12-12 1997-10-07 Glaxo Group Limited Aerosol formulations containing P134a and salbutamol
US5744123A (en) * 1991-12-12 1998-04-28 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicaments
US5916540A (en) 1994-10-24 1999-06-29 Glaxo Group Limited Aerosol formulations containing P134A and/or P227 and particulate medicament
US5658549A (en) * 1991-12-12 1997-08-19 Glaxo Group Limited Aerosol formulations containing propellant 134a and fluticasone propionate
US5736124A (en) * 1991-12-12 1998-04-07 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicament
IL104068A (en) * 1991-12-12 1998-10-30 Glaxo Group Ltd Pharmaceutical preparations in a spray without surfactant containing 1, 1, 1, 2 tetrafluoroethane or 1,1,2,3,3 petafluor N propane as propellant
CA2421976C (fr) 1991-12-12 2004-04-20 Glaxo Group Limited Medicaments
GB9202519D0 (en) * 1992-02-06 1992-03-25 Glaxo Group Ltd Medicaments
US5833950A (en) * 1992-07-31 1998-11-10 Glaxo Group Limited Aerosol formulations containing beclomethasone dipropionate-1, 1, 1, 2-tetrafluoroethane solvate
MX9304585A (es) * 1992-07-31 1994-03-31 Glaxo Group Ltd Formulacion farmaceutica en aerosol, lata adecuada para liberar la formulacion e inhalador de dosis dosificada que comprende la lata.
US5593661A (en) * 1993-03-29 1997-01-14 Henry; Richard A. Lidocaine aerosol anaesthetic
CA2178473C (fr) * 1993-12-20 2004-08-24 Tsi-Zong Tzou Compositions d'aerosols a base de flunisolide
PE44995A1 (es) * 1994-01-27 1995-12-18 Schering Corp Furoato de mometasona para el tratamiento de las enfermedades pulmonares y de las vias respiratorias
US5653961A (en) * 1995-03-31 1997-08-05 Minnesota Mining And Manufacturing Company Butixocort aerosol formulations in hydrofluorocarbon propellant
US5874481A (en) * 1995-06-07 1999-02-23 Alliance Pharmaceutical Corp. Fluorochemical solutions for the delivery of lipophilic pharmaceutical agents
TR199701711T1 (xx) * 1995-06-27 1998-05-21 Boehringer Ingelheim Kg. Aerosollerin imalat� i�in yeni stabil ila� bile�imleri.
DE19616573C2 (de) 1996-04-25 1999-03-04 Pari Gmbh Verwendung unterkritischer Treibmittelmischungen und Aerosole für die Mikronisierung von Arzneimitteln mit Hilfe dichter Gase
GB9616237D0 (en) 1996-08-01 1996-09-11 Norton Healthcare Ltd Aerosol formulations
JPH1067655A (ja) * 1996-08-23 1998-03-10 Nippon Hoechst Marion Roussel Kk 喘息治療用エアゾール剤
US6068832A (en) * 1996-08-29 2000-05-30 Schering Corporation Chlorofluorocarbon-free mometasone furoate aerosol formulations
IES80485B2 (en) * 1996-12-04 1998-08-12 Bioglan Ireland R & D Ltd Pharmaceutical compositions and devices for their administration
US6120752A (en) * 1997-05-21 2000-09-19 3M Innovative Properties Company Medicinal aerosol products containing formulations of ciclesonide and related steroids
US20010031244A1 (en) * 1997-06-13 2001-10-18 Chiesi Farmaceutici S.P.A. Pharmaceutical aerosol composition
GB2326334A (en) † 1997-06-13 1998-12-23 Chiesi Farma Spa Pharmaceutical aerosol compositions
GB2332372B (en) * 1997-12-08 2002-08-14 Minnesota Mining & Mfg Pharmaceutical aerosol compositions
US6086376A (en) * 1998-01-30 2000-07-11 Rtp Pharma Inc. Dry aerosol suspension of phospholipid-stabilized drug microparticles in a hydrofluoroalkane propellant
GB9807232D0 (en) 1998-04-03 1998-06-03 Univ Cardiff Aerosol composition
US6264923B1 (en) 1998-05-13 2001-07-24 3M Innovative Properties Company Medicinal aerosol formulation of ciclesonide and related compounds
US6451285B2 (en) 1998-06-19 2002-09-17 Baker Norton Pharmaceuticals, Inc. Suspension aerosol formulations containing formoterol fumarate and a fluoroalkane propellant
IT1303788B1 (it) 1998-11-25 2001-02-23 Chiesi Farma Spa Formulazioni di aerosol medicinali.
US6004537A (en) * 1998-12-18 1999-12-21 Baker Norton Pharmaceuticals, Inc. Pharmaceutical solution aerosol formulations containing fluoroalkanes, budesonide and formoterol
US6290930B1 (en) 1998-12-18 2001-09-18 Baker Norton Pharmaceuticals, Inc. Pharmaceutical solution aerosol formulations containing fluoroalkanes and budesonide
EP1248597B1 (fr) * 1999-12-24 2005-03-30 Glaxo Group Limited Formulation pharmaceutique en aerosol de salmeterol et de propionate de fluticasone
FR2813877B1 (fr) 2000-09-11 2002-12-06 Cezus Cie Europ Du Zirconium Procede de separation de metaux tels que le zirconium et l'hafnium
GB0208742D0 (en) 2002-04-17 2002-05-29 Bradford Particle Design Ltd Particulate materials
EP1340503A1 (fr) * 2002-03-01 2003-09-03 CHIESI FARMACEUTICI S.p.A. Formule d'une solution pour aerosol contenant des dérivés d'esters de 3,17 estratrien pour administration pulmonale
KR20050045946A (ko) 2002-06-25 2005-05-17 애크럭스 디디에스 피티와이 리미티드 비정질 약학적 조성물을 이용한 경피전달속도의 제어
AUPS317302A0 (en) * 2002-06-25 2002-07-18 Drug Delivery Solutions Pty Ltd Metastable pharmaceutical compositions
AU2008214205B2 (en) 2007-02-11 2014-04-24 Map Pharmaceuticals, Inc. Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile
US8652443B2 (en) 2008-02-14 2014-02-18 Precision Dermatology, Inc. Foamable microemulsion compositions for topical administration
AR079451A1 (es) 2009-12-18 2012-01-25 Nycomed Gmbh Compuestos 3,4,4a,10b-tetrahidro-1h-tiopirano[4,3-c]isoquinolina
JP6050236B2 (ja) 2010-10-12 2016-12-21 アイバックス ファーマシューティカルズ アイルランド 鼻内噴霧装置
US20140113877A1 (en) 2011-06-15 2014-04-24 Takeda Gmbh Novel 3,4,4a,10b-tetrahydro-1h-thiopyrano[4,3-c] isoquinoline compounds
KR20140037195A (ko) 2011-06-17 2014-03-26 다케다 게엠베하 신규 프탈라지논-피롤로피리미딘카복스아미드 유도체
EP2744479A1 (fr) 2011-08-18 2014-06-25 Takeda GmbH Produit aérosol pharmaceutique pour l'administration par inhalation orale ou nasale
CN104039150A (zh) * 2011-09-20 2014-09-10 军士宠物护理用品股份有限公司 介素组合物及其在调节不同脊椎动物的行为中的用途
US9480688B2 (en) 2011-09-20 2016-11-01 Sergeant's Pet Care Products, Inc. Pheromone compositions and their use to modify behavior in different vertebrate species
WO2018069210A1 (fr) 2016-10-10 2018-04-19 Takeda Gmbh Tétrahydrofuro [3,4-c] isoquinolines en tant qu'inhibiteurs de pde4
US20200268706A1 (en) * 2017-02-27 2020-08-27 Gregory LEVITIN Combination of furosemide and steroids and application system therefor

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8432063D0 (en) * 1984-12-19 1985-01-30 Riker Laboratories Inc Physically modified steroids
DE4003270A1 (de) * 1990-02-03 1991-08-08 Boehringer Ingelheim Kg Neue treibgase und ihre verwendung in arzneimittelzubereitungen
IE67185B1 (en) * 1990-02-02 1996-03-06 Fisons Plc Propellant compositions
DE4003272A1 (de) * 1990-02-03 1991-08-08 Boehringer Ingelheim Kg Neue treibgasmischungen und ihre verwendung in arzneimittelzubereitungen

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7101534B1 (en) 1991-12-18 2006-09-05 3M Innovative Properties Company Suspension aerosol formulations
US6433040B1 (en) 1997-09-29 2002-08-13 Inhale Therapeutic Systems, Inc. Stabilized bioactive preparations and methods of use
US6565885B1 (en) 1997-09-29 2003-05-20 Inhale Therapeutic Systems, Inc. Methods of spray drying pharmaceutical compositions
US6638495B2 (en) 1997-09-29 2003-10-28 Nektar Therapeutics Stabilized preparation for use in metered dose inhalers
US8080263B2 (en) 1997-09-29 2011-12-20 Novartis Ag Dispersion for pulmonary delivery of a bioactive agent
US8168223B1 (en) 1997-09-29 2012-05-01 Novartis Pharma Ag Engineered particles and methods of use
US9554993B2 (en) 1997-09-29 2017-01-31 Novartis Ag Pulmonary delivery particles comprising an active agent
US7220403B2 (en) 1999-09-11 2007-05-22 Glaxo Group Limited Pharmaceutical formulation of fluticasone propionate
US8404217B2 (en) 2000-05-10 2013-03-26 Novartis Ag Formulation for pulmonary administration of antifungal agents, and associated methods of manufacture and use
US8709484B2 (en) 2000-05-10 2014-04-29 Novartis Ag Phospholipid-based powders for drug delivery
US8877162B2 (en) 2000-05-10 2014-11-04 Novartis Ag Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery
US9439862B2 (en) 2000-05-10 2016-09-13 Novartis Ag Phospholipid-based powders for drug delivery
US8715623B2 (en) 2001-12-19 2014-05-06 Novartis Ag Pulmonary delivery of aminoglycoside
US9421166B2 (en) 2001-12-19 2016-08-23 Novartis Ag Pulmonary delivery of aminoglycoside
US8435497B2 (en) 2003-06-13 2013-05-07 Takeda Gmbh Formoterol of and ciclesonide combination
US8371292B2 (en) 2003-09-16 2013-02-12 Nycomed Gmbh Use of ciclesonide for the treatment of respiratory diseases

Also Published As

Publication number Publication date
AU9087391A (en) 1992-05-20
DK0553298T3 (da) 1995-04-18
CA2094266A1 (fr) 1992-04-19
EP0553298A1 (fr) 1993-08-04
JPH10182467A (ja) 1998-07-07
CA2094266C (fr) 1999-06-01
HK130397A (en) 1997-09-19
JPH06501710A (ja) 1994-02-24
BR1100339A (pt) 2000-07-18
ATE114112T1 (de) 1994-12-15
WO1992006675A1 (fr) 1992-04-30
ES2064160T3 (es) 1995-01-16
JP2769925B2 (ja) 1998-06-25
AU658854B2 (en) 1995-05-04
DE69105212D1 (de) 1994-12-22
DE69105212T2 (de) 1995-03-23
NZ240237A (en) 1994-06-27

Similar Documents

Publication Publication Date Title
EP0553298B1 (fr) Formulation d'aerosol contenant du beclomethasone 17,21 dipropionate
US6346232B1 (en) Method of forming conductive lines
EP0755247B1 (fr) Aerosols medicamenteux contenant un gaz propulseur a base d'hydrofluorocarbones
EP0526481B1 (fr) Emploi de fluorotensioactifs solubles dans la preparation de formulations d'aerosols doseurs
KR100428914B1 (ko) 에어로졸약물제제
EP0617610B1 (fr) Formulations d'aerosol en suspension
EP1100465B1 (fr) Formulations pour aerosols a usage medical
EP0536204B1 (fr) Emploi de tensio-actifs fluores solubles dans la preparation de compositions pour aerosol doseur
AU776257B2 (en) Pharmaceutical aerosol formulations containing fluoroalkanes, budesonide and formoterol
EP1372608B1 (fr) Formulations aerosol medicales
EP0918507B2 (fr) Formulations d'aerosol
EP0932397B1 (fr) Formulations pour aerosold medicinaux contenant du budesonide
JPH10506887A (ja) 医薬品
WO2001089480A1 (fr) Preparation en solution pharmaceutique stable pour aerosols-doseurs sous pression
US20100095963A1 (en) Pharmaceutical compositions
Tzou et al. Drug form selection in albuterol‐containing metered‐dose inhaler formulations and its impact on chemical and physical stability
PL189036B1 (pl) Zawiesinowy preparat aerozolowy zawierający pirośluzan mometazonu
KR0175164B1 (ko) 에어로졸 약물 제제
MXPA01006082A (en) Pharmaceutical aerosol formulations containing fluoroalkanes, budesonide and formoterol

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19930407

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB IT LI LU NL SE

17Q First examination report despatched

Effective date: 19931228

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE CH DE DK ES FR GB IT LI LU NL SE

REF Corresponds to:

Ref document number: 114112

Country of ref document: AT

Date of ref document: 19941215

Kind code of ref document: T

REF Corresponds to:

Ref document number: 69105212

Country of ref document: DE

Date of ref document: 19941222

ITF It: translation for a ep patent filed

Owner name: ING. C. GREGORJ S.P.A.

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2064160

Country of ref document: ES

Kind code of ref document: T3

EAL Se: european patent in force in sweden

Ref document number: 92900942.1

ET Fr: translation filed
REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

PLBI Opposition filed

Free format text: ORIGINAL CODE: 0009260

26 Opposition filed

Opponent name: NORTON HEALTHCARE LTD

Effective date: 19950814

Opponent name: JAGO PHARMA AG

Effective date: 19950812

NLR1 Nl: opposition has been filed with the epo

Opponent name: NORTON HEALTHCARE LTD

Opponent name: JAGO PHARMA AG

PLBF Reply of patent proprietor to notice(s) of opposition

Free format text: ORIGINAL CODE: EPIDOS OBSO

PLBF Reply of patent proprietor to notice(s) of opposition

Free format text: ORIGINAL CODE: EPIDOS OBSO

PLAW Interlocutory decision in opposition

Free format text: ORIGINAL CODE: EPIDOS IDOP

APAC Appeal dossier modified

Free format text: ORIGINAL CODE: EPIDOS NOAPO

APAE Appeal reference modified

Free format text: ORIGINAL CODE: EPIDOS REFNO

PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO

R26 Opposition filed (corrected)

Opponent name: SKYEPHARMA AG * 950814 NORTON HEALTHCARE LTD

Effective date: 19950812

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 19980917

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SE

Payment date: 19980918

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 19980921

Year of fee payment: 8

Ref country code: DK

Payment date: 19980921

Year of fee payment: 8

Ref country code: DE

Payment date: 19980921

Year of fee payment: 8

Ref country code: AT

Payment date: 19980921

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 19981005

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 19981008

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: ES

Payment date: 19981015

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 19981026

Year of fee payment: 8

NLR1 Nl: opposition has been filed with the epo

Opponent name: NORTON HEALTHCARE LTD

Opponent name: SKYEPHARMA AG

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: LU

Payment date: 19981103

Year of fee payment: 8

APAC Appeal dossier modified

Free format text: ORIGINAL CODE: EPIDOS NOAPO

RDAH Patent revoked

Free format text: ORIGINAL CODE: EPIDOS REVO

RDAG Patent revoked

Free format text: ORIGINAL CODE: 0009271

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: PATENT REVOKED

27W Patent revoked

Effective date: 19990429

GBPR Gb: patent revoked under art. 102 of the ep convention designating the uk as contracting state

Free format text: 990429

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

REG Reference to a national code

Ref country code: GB

Ref legal event code: 775L

Ref country code: GB

Ref legal event code: 7722

Free format text: APPEAL TO THE COURT OF APPEAL DISMISSED BY ORDER OF THE COURT DATED 08 FEBRUARY 1999. NB. PATENT REVOKED BY EPO ON 29 APRIL 1999.

NLR2 Nl: decision of opposition
APAH Appeal reference modified

Free format text: ORIGINAL CODE: EPIDOSCREFNO